TY - JOUR
T1 - β-catenin-promoted cholesterol metabolism protects against cellular senescence in naked mole-rat cells
AU - Chee, Woei Yaw
AU - Kurahashi, Yuriko
AU - Kim, Junhyeong
AU - Miura, Kyoko
AU - Okuzaki, Daisuke
AU - Ishitani, Tohru
AU - Kajiwara, Kentaro
AU - Nada, Shigeyuki
AU - Okano, Hideyuki
AU - Okada, Masato
N1 - Funding Information:
The authors acknowledge the NGS core facility of the Genome Information Research Center at the Research Institute for Microbial Diseases of Osaka University for support with RNA sequencing and data analysis, and Dr. Hiroko Ohmori from the Core Instrumentation Facility, Research Institute for Microbial Diseases, for conducting TEM observations of cells. Raw RNA-seq data related to this study were submitted under GEO accession number GSE147871. This work was supported by JPSP KAKENHI (Grant numbers 19H03504 and 19H04962 to M.O.; 19H03412 to T.I.; and 18H02365 to K.M.) and AMED (JP19gm5010001 to T.I., and JP19gm5010001 and 19gm0704040 to K.M.).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - The naked mole-rat (NMR; Heterocephalus glaber) exhibits cancer resistance and an exceptionally long lifespan of approximately 30 years, but the mechanism(s) underlying increased longevity in NMRs remains unclear. In the present study, we report unique mechanisms underlying cholesterol metabolism in NMR cells, which may be responsible for their anti-senescent properties. NMR fibroblasts expressed β-catenin abundantly; this high expression was linked to increased accumulation of cholesterol-enriched lipid droplets. Ablation of β-catenin or inhibition of cholesterol synthesis abolished lipid droplet formation and induced senescence-like phenotypes accompanied by increased oxidative stress. β-catenin ablation downregulated apolipoprotein F and the LXR/RXR pathway, which are involved in cholesterol transport and biogenesis. Apolipoprotein F ablation also suppressed lipid droplet accumulation and promoted cellular senescence, indicating that apolipoprotein F mediates β-catenin signaling in NMR cells. Thus, we suggest that β-catenin in NMRs functions to offset senescence by regulating cholesterol metabolism, which may contribute to increased longevity in NMRs.
AB - The naked mole-rat (NMR; Heterocephalus glaber) exhibits cancer resistance and an exceptionally long lifespan of approximately 30 years, but the mechanism(s) underlying increased longevity in NMRs remains unclear. In the present study, we report unique mechanisms underlying cholesterol metabolism in NMR cells, which may be responsible for their anti-senescent properties. NMR fibroblasts expressed β-catenin abundantly; this high expression was linked to increased accumulation of cholesterol-enriched lipid droplets. Ablation of β-catenin or inhibition of cholesterol synthesis abolished lipid droplet formation and induced senescence-like phenotypes accompanied by increased oxidative stress. β-catenin ablation downregulated apolipoprotein F and the LXR/RXR pathway, which are involved in cholesterol transport and biogenesis. Apolipoprotein F ablation also suppressed lipid droplet accumulation and promoted cellular senescence, indicating that apolipoprotein F mediates β-catenin signaling in NMR cells. Thus, we suggest that β-catenin in NMRs functions to offset senescence by regulating cholesterol metabolism, which may contribute to increased longevity in NMRs.
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U2 - 10.1038/s42003-021-01879-8
DO - 10.1038/s42003-021-01879-8
M3 - Article
C2 - 33742113
AN - SCOPUS:85102685761
SN - 2399-3642
VL - 4
JO - Communications biology
JF - Communications biology
IS - 1
M1 - 357
ER -
